Kidney Cancer, Renal Cell Carcinoma
Conditions
Keywords
Renal Mass, Clear Cell Renal Cell Carcinoma, Cancer of Kidney, Kidney Cancer, Neoplasms, cG250, antibody, monoclonal, Iodine 124, Positron-Emission Tomography, Kidney, Renal Cancer, Renal Neoplasms
Brief summary
This is a multicenter Phase III study to demonstrate the diagnostic utility of 124I-cG250 PET/CT pre-surgical imaging in patients with operable renal masses.
Detailed description
A preoperative 124I-cG250 PET scan may distinguish between clear cell and non-clear cell renal carcinoma in patients with renal masses. Studies of imaging characteristics of 124I by a variety of PET cameras, quantification of tumor uptake of 124I-labeled antibody and correlation with biopsy measurement of tumor and normal tissue have met with encouraging results. As clear cell renal cancers are associated with an aggressive phenotype their a priori determination may help guide appropriate surgical/therapeutic management.
Interventions
i.v. and PET/CT scan 4+/-2 days after administration
PROCEDURECT
contrast enhanced CT scan
Sponsors
Heidelberg Pharma AG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is over 18 years of age. * Presence of a renal mass. * Scheduled for surgical resection of renal mass (partial or total nephrectomy, open or laparoscopic technique). * Expected survival of at least 3 months. * Eastern Cooperative Oncology Group (ECOG) performance status \< 2. * The following laboratory results should be within the following limits within the last 2 weeks prior to study day 1: * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L * Platelet count ≥ 100 x 109/L * Serum bilirubin ≤ 2.0 mg/dL * Aspartate aminotransaminase (AST) ≤ 2.5 x ULN * Alanine aminotransferase (ALT) ≤ 2.5 x ULN * Serum creatinine ≤ 2.0 mg/dL (calculated creatinine clearance \>45 ml/min) * Negative serum pregnancy test; to be performed on female patients of childbearing potential within 24 hours prior to receiving investigational product. All females of childbearing potential must indicate intent to avoid pregnancy and must use an accepted, effective method of contraception for the duration of the study. * Recovered from toxicity of any prior therapy. * Able and willing to give valid written informed consent.
Exclusion criteria
* Metastasis of primary tumor other than Renal Cell Carcinoma (RCC). * Prior history of malignancy within the last 5 years. * Prior exposure to murine proteins or chimeric antibodies. * Intercurrent medical condition that may limit the amount of antibody to be administered. * Intercurrent medical condition that renders the patient ineligible for surgery. * New York Heart Association Class III/IV cardiac disease. * History of autoimmune hepatitis. * Chemotherapy, radiotherapy, or immunotherapy within 4 weeks prior to 124I-cG250 infusion on day 1. * Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study. * Lack of availability for immunological and clinical follow-up assessments. * Participation in any other clinical trial involving another investigational product within 4 weeks prior to enrolment. * Women who are pregnant or breastfeeding. * Allergy to iodine, hyperthyroidism, or Grave's Disease. * Known allergic reaction to human serum albumin. * Contraindication for contrast-enhanced CT or PET/CT. * Contraindication to potassium iodide intake (see package insert).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity and Specificity of 124I-cG250 PET/CT Versus Diagnostic CT. | 6 months | Average estimate of three independent, blinded central readers per imaging modality on the proportion of participants that were correctly identified on the 124I-cG250 PET/CT Images of having (sensitivity) or not having (specificity) clear cell renal carcinoma (ccRCC) compared to CT images. Histopathology provided the standard-of-truth because it is the only definitive method for accurately identifying ccRCC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Accuracy of 124I-cG250 PET/CT Imaging Versus Diagnostic CT Imaging | 6 months | The Accuracy is the proportion of participants with correct determinations of 124I-cG250 PET/CT imaging compared to diagnostic CT Imaging in the detection of ccRCC as confirmed by histopathology diagnoses. The numbers represent the average estimate of three independent, blinded central readers per imaging modality. For the secondary efficacy variables no 95% CIs for differences of averages were calculated. |
| Positive Predictive Value (PPV) | 6 months | The Positive Predictive Value (PPV) reflects the Proportion of positive results that are true positive. The PPV of 124I-cG250 PET/CT imaging compared to diagnostic CT Imaging in the detection of ccRCC as confirmed by histopathology diagnoses. The numbers represent the average estimate of three independent, blinded central readers per imaging modality. For the secondary efficacy variables no 95% CIs for differences of averages were calculated. |
| Negative Predictive Value (NPV) | 6 months | Negative Predictive Value (NPV) reflects the proportion of negative results that are true negatives. The NPV of 124I-cG250 PET/CT imaging compared to diagnostic CT Imaging in the detection of ccRCC as confirmed by histopathology diagnoses. The numbers represent the average estimate of three independent, blinded central readers per imaging modality. For the secondary efficacy variables no 95% CIs for differences of averages were calculated. |
Countries
United States
Participant flow
Recruitment details
226 subjects were enrolled at 14 study sites in the USA.
Participants by arm
| Arm | Count |
|---|---|
| PET/CT Versus CT All subjects were scheduled to receive a PET/CT and a diagnostic CT | 226 |
| Total | 226 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Miscellaneous reasons | 9 |
| Overall Study | Withdrawal by Subject | 13 |
Baseline characteristics
| Characteristic | PET/CT Versus CT |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 59 Participants |
| Age, Categorical Between 18 and 65 years | 167 Participants |
| Age, Continuous | 56.1 years STANDARD_DEVIATION 12.01 |
| Region of Enrollment United States | 226 participants |
| Sex: Female, Male Female | 84 Participants |
| Sex: Female, Male Male | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 191 / 226 |
| serious Total, serious adverse events | 33 / 226 |
Outcome results
Primary
Sensitivity and Specificity of 124I-cG250 PET/CT Versus Diagnostic CT.
Average estimate of three independent, blinded central readers per imaging modality on the proportion of participants that were correctly identified on the 124I-cG250 PET/CT Images of having (sensitivity) or not having (specificity) clear cell renal carcinoma (ccRCC) compared to CT images. Histopathology provided the standard-of-truth because it is the only definitive method for accurately identifying ccRCC.
Time frame: 6 months
Population: ITD (Intend-to-Diagnose) observed case: All subjects who were enrolled and infused with the investigational product and who had a standard-of-truth (histopathology) result and images evaluated as readable by the blinded readers
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sensitivity CT | Sensitivity and Specificity of 124I-cG250 PET/CT Versus Diagnostic CT. | 0.76 Proportion of participants |
| Sensitivity PET/CT | Sensitivity and Specificity of 124I-cG250 PET/CT Versus Diagnostic CT. | 0.86 Proportion of participants |
| Specificity PET/CT | Sensitivity and Specificity of 124I-cG250 PET/CT Versus Diagnostic CT. | 0.86 Proportion of participants |
| Specificity CT | Sensitivity and Specificity of 124I-cG250 PET/CT Versus Diagnostic CT. | 0.47 Proportion of participants |
p-value: 0.023McNemar
p-value: <0.01McNemar
Secondary
Accuracy of 124I-cG250 PET/CT Imaging Versus Diagnostic CT Imaging
The Accuracy is the proportion of participants with correct determinations of 124I-cG250 PET/CT imaging compared to diagnostic CT Imaging in the detection of ccRCC as confirmed by histopathology diagnoses. The numbers represent the average estimate of three independent, blinded central readers per imaging modality. For the secondary efficacy variables no 95% CIs for differences of averages were calculated.
Time frame: 6 months
Population: ITD (Intend-to-Diagnose) observed case: All subjects who were enrolled and infused with the investigational product and who had a standard-of-truth (histopathology) result and images evaluated as readable by the blinded readers
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sensitivity CT | Accuracy of 124I-cG250 PET/CT Imaging Versus Diagnostic CT Imaging | 0.86 Proportion of participants |
| Sensitivity PET/CT | Accuracy of 124I-cG250 PET/CT Imaging Versus Diagnostic CT Imaging | 0.68 Proportion of participants |
Secondary
Negative Predictive Value (NPV)
Negative Predictive Value (NPV) reflects the proportion of negative results that are true negatives. The NPV of 124I-cG250 PET/CT imaging compared to diagnostic CT Imaging in the detection of ccRCC as confirmed by histopathology diagnoses. The numbers represent the average estimate of three independent, blinded central readers per imaging modality. For the secondary efficacy variables no 95% CIs for differences of averages were calculated.
Time frame: 6 months
Population: ITD (Intend-to-Diagnose) observed case: All subjects who were enrolled and infused with the investigational product and who had a standard-of-truth (histopathology) result and images evaluated as readable by the blinded readers
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sensitivity CT | Negative Predictive Value (NPV) | 0.69 Proportion of participants |
| Sensitivity PET/CT | Negative Predictive Value (NPV) | 0.41 Proportion of participants |
Secondary
Positive Predictive Value (PPV)
The Positive Predictive Value (PPV) reflects the Proportion of positive results that are true positive. The PPV of 124I-cG250 PET/CT imaging compared to diagnostic CT Imaging in the detection of ccRCC as confirmed by histopathology diagnoses. The numbers represent the average estimate of three independent, blinded central readers per imaging modality. For the secondary efficacy variables no 95% CIs for differences of averages were calculated.
Time frame: 6 months
Population: ITD (Intend-to-Diagnose) observed case: All subjects who were enrolled and infused with the investigational product and who had a standard-of-truth (histopathology) result and images evaluated as readable by the blinded readers
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sensitivity CT | Positive Predictive Value (PPV) | 0.94 Protportion of participants |
| Sensitivity PET/CT | Positive Predictive Value (PPV) | 0.80 Protportion of participants |